A method of endoscopically resecting a small lesion, such as a polyp or cancer, formed on the mucosa of the gastrointestinal tract, such as the stomach or intestine, without performing laparotomy (the method is called endoscopic mucosal resection), is performed clinically. During this operation, the site of the mucosal lesion does not necessarily protrude clearly. Moreover, the surface of the mucosa is slippery. Thus, resecting the lesion by remote control while observing it through the endoscope involves corresponding technical difficulty, and may cause a risk, such as the remaining lesion after resection, or a surgery-associated complication such as bleeding or perforation.
To improve the resection efficiency, operability and safety of endoscopic mucosal resection, it has been common practice to inject physiological saline into the stratum below the site scheduled for resection, thereby elevating and protruding (hereinafter referred to simply as “elevating” or “elevation” according to the context) the lesion, and resect the lesion. According to this method, however, the elevated site is easily deformable upon compression for resection. Also, the level of the elevation is so low that the elevation dissipates rapidly over time and disappears. Thus, it has been difficult to resect the targeted site reliably.
Alternatively, a hypertonic saline solution or a 50% glucose solution has been used for more persistent elevation. However, the elevation sustaining effect of such a hypertonic solution is not very high, and is even injurious to the tissue. The application of the hypertonic solution may cause perforation to the large intestine with a small wall thickness, and is problematical in safety. Under these circumstances, the inventor of the present invention previously proposed the injection of low molecular weight hyaluronic acid with an average molecular weight of about 800,000 (Gastrointest. Endosc. 50(5), 701-704, 1999; Gastrointest. Endosc. 50(2), 251-256, 1999; Japanese Patent Application No. 2000-37240). Hyaluronic acid, existent in large amounts in vivo, has a high molecular weight, and shows high viscosity at low concentrations, thus minimally affecting osmotic pressure. When diluted with physiological saline, therefore, hyaluronic acid can form a preparation isotonic to body fluids, and can give a solution with in vivo safety which is injected submucosally during endoscopic mucosal resection (EMR).
The above method, proposed by the present inventor, improves the level of elevation and the duration of elevation of the lesion, and increases the efficiency of resection, as compared with the conventional method. However, the duration of elevation of the lesion is at most about 10 to 20 minutes under favorable conditions (concentration of 0.5 w/v %). This elevation time is not entirely satisfactory when a surgical operation takes time as in resecting a lesion of 20 mm or larger in one piece. Development of an injectable preparation presenting a longer elevation time has been desired.
A parenteral solution (injectable preparation as a solution) for injecting high molecular weight hyaluronic acid into the intra-articular space is known (Japanese Unexamined Patent Publication No. 1996-188534). However, an injection needle for this injectable preparation is so short in length that the injection pressure of hyaluronic acid is not very problematical. In the case of an injection needle for an endoscope, on the other hand, the effective length of the tube of the injection needle is usually as long as 1,000 mm or more, so that the injection pressure of the injectable preparation is a major problem from the point of view of operability.
Thus, the development of an injectable preparation, which can prolong the elevation time as stated earlier, does not involve too high an injection pressure, and is not problematical in operability, is desired.